Apparatus for automated processing biological samples

ABSTRACT

The present invention concerns an apparatus for automatic processing at least one biological sample accommodated on a carrier member, such as a slide by applying a predetermined amount of reagents in a predetermined sequence according to a processing protocol, said apparatus comprising; a housing frame; at least one processing section for accommodating at least one slide, the at least one processing section is provided within the housing; a hood cover protecting the at least one processing section in said housing; wherein the hood cover completely encloses the processing section defining an interior space; and wherein the apparatus further comprises climate control device provided to control the environment within the interior space.

This application is the United States National Stage of InternationalApplication No. PCT/US2003/040520, filed Dec. 19, 2003 which claims thebenefit under 35 U.S.C. 119(e) of U.S. Provisional Application No.60/435,601, filed Dec. 20, 2002, each hereby incorporated by referenceherein.

TECHNICAL FIELD

The present invention relates to a method and an apparatus for automaticprocessing of at least one biological sample accommodated on a carriermember, such as microscopic slide, by applying a predetermined amount ofreagents in a sequence according to a processing protocol, wherein atleast one slide is provided in a slide rack assembly.

This application relates to the field of sample processing systems andmethods of processing samples. The present invention may be directed tothe automated processing, treatment, or even staining of samplesarranged on carriers, such as microscope slides, and in someembodiments, directed to the continuous or batch processing of samplesand carriers, as well as washing elements of a sampling system.Embodiments may further relate to control systems for sample processingand data acquisition, data maintenance, and data retrieval for sampleprocessing. Applications to which the present invention may especiallyrelate include cytology, immunohistochemistry, in-situ hybridization,fluorescent in-situ hybridization, special staining, and microarrays, aswell as potentially other chemical and biological applications.

BACKGROUND

The biological sample may suitably be selected from histologicalmaterial, including formalin fixed and paraffin embedded material,cytological material, fine needle aspirates, cell smears, exfoliativecytological specimens, touch preparations, bone marrow specimens, sputumsamples, expectorates, oral swabs, laryngeal swabs, vaginal swabs,bronchial aspirates, bronchial lavage, gastric lavage, and body fluids.Such may be subjected to various treatments.

Sample processing in immunohistochemical (IHC) applications and in otherchemical and biological analyses may require one or a number of variousprocessing sequences or protocols as part of an analysis of one or moresamples. The sample processing sequences or protocols may be defined bythe individual or organization requesting an analysis, such as apathologist or histologist of a hospital, and may be further defined bythe dictates of a particular analysis to be performed.

In preparation for sample analysis, a biological sample may be acquiredby known sample acquisition techniques and may comprise, for example inIHC applications, tissues generally or even in some applications one ora plurality of isolated cells, such as in microarray samples, and may bepresented on a sample carrier such as a microscope slide. Furthermore,the sample may be presented on the carrier variously and potentially insome form of preservation. As one example, a human biopsi sample may befixed and embedded in a suitable media like paraffin or epon, beforebeing mounted onto a carrier. The sample may be treated according to theprotocol, which may include the following non limiting procedural steps:deparaffination, antigen retrieval, denaturing, washing, incubation withvarious immunological reagents, molecular probes or dyes, strigency washor counterstaining.

Histological cytological, ISH, IHC special stains and otherapplications, for example, may require processing sequences or protocolsthat comprise many and laborious steps such as deparaffinization, targetretrieval, and staining. Such steps are not special for ISH procedures,but goes for IHC, cytological, specials or ISH stainings. Previously, insome applications, these steps may have been performed manually,potentially creating a time-intensive protocol and necessitatingpersonnel to be actively involved in the sample processing. Attemptshave been made to automate sample processing to address the need forexpedient sample processing and a less manually burdensome operation.However, such previous efforts may have not fully addressed the needsfor an automated sample processing system. Previous efforts to automatesample processing may be deficient in several aspects that prevent morerobust automated sample processing, such as: the lack of sufficientcomputer control and monitoring of sample processing; the lack ofinformation sharing for processing protocol and processing status,especially for individual samples; the lack of diagnostic capabilities;and the lack of real-time or adaptive capabilities for multiple samplebatch processing.

From U.S. Pat. No. 5,839,091 an automated sample processing for samplespresented on carriers such as slides is known. In this apparatus, anarray of slides is stained by a robotic device delivering reagents ontothe slides. The staining apparatus is provided with a lid cover, whichprovides a protective cover of the biological samples on the carriers inthe apparatus during the staining processes as well as containing stainsof the some times hazardous reagent materials within the apparatus andpreventing operators from being exposed to such stains.

Slides can be any suitable solid or semi solid support for thebiological sample. In particular, the support may be a microscope slide,a membrane, a filter, a polymer slide, a chamber slide, a dish, or apetridish

Some staining processes involve the use of hazardous materials, such astoxic materials. These materials may be collected in special containersin order to ensure safe handling of the waste material. However, thisdoes not sufficiently protect the laboratory environment in which theapparatus is placed from being contaminated with toxic material.Moreover, in some staining processes or other treatments in theapparatus heat is applied. This increases the risk of vaporisingreagents which then may escape to the outside of the apparatus.

In the apparatuses known in the art, a protective hood or similarplastic cover is put over the staining apparatus in order to shield offthe biological samples during the staining. In this known technique, onerisk is the drying out of slides and lack of control of airspeed andtemperature.

DISCLOSURE OF INVENTION

On this background, it is an object of the invention to provide anapparatus for automatic staining of biological samples, in which thehazardous materials and toxic or otherwise damaging fumes are containedand automatically handled, so that operators need not be involved in thehandling of such types of materials.

The invention consists of a method and an apparatus for automaticstaining at least one biological sample accommodated on a carrier slideby applying a predetermined amount of reagents in a predeterminedsequence according to a staining protocol, said apparatus comprising: ahousing frame; at least one staining section for accommodating at leastone slide, said at least one staining section is provided within saidhousing; a hood cover protecting said at least one staining section insaid housing; wherein the hood cover completely encloses the stainingsection defining an interior space; and wherein the apparatus furthercomprises climate control device that provide control of the environmentwithin said interior space; and sensor device to provide feedbacksignals to the climate control means.

In the staining apparatus, fumes from the reagents and other processingliquids used in the apparatus for performing the treatment of thebiological samples are present. In an apparatus according to theinvention, these fumes may be exhausted from the interior space of theapparatus, just as the climate in the apparatus may be controlled. Inparticular, in order to avoid the volatile fumes from escaping into thesurroundings, the climate control device preferably includes a pressurecontrol device that can ensure a slight sub-pressure within the interiorspace. By maintaining a slight sub-pressure inside the apparatus, thefumes are kept inside in the interior space, from where the climatecontrol system may remove the volatile fumes. These fumes mayadvantageously be collected in suitable storage or otherwise be disposedof.

Advantageously, the climate control device may also include humiditycontrol within the interior space. This makes an apparatus according tothe invention more suitable for some special sample treatmentapplications, just as the climate requirement inside the laboratorywhere the apparatus is placed may be less strict. Moreover, the climatecontrol device may preferably also include a temperature control devicethat can control the ambient temperature of the air within the interiorspace.

Climate control, especially control of temperature and humidity isimportant for ensuring standardized and reproducible staining protocols,as the biological samples can easily dry out or changes properties,including morphology and antigenicity. Also, the controlled environmentcan ensure uniform chemical reaction conditions on the slides during thestaining protocol.

The climate control device in an apparatus according to the inventionmay include an exhaustion device that can remove fumes from the interiorspace. These exhaustion devices are preferably adapted to draw air froman outlet positioned below the level in which the at least one slide isaccommodated. Hereby, fumes are drawn away from the hood and the slides.This may reduce any risk of cross-contamination. Cross contaminationcould be a problem, as some fumes can adsorb to the biological sample,resulting in a change of properties. Especially hydrophobic, acidic,basic, strong chaotropic or otherwise reactive or corrosive fumes cancause serious and unwanted cross contamination.

The sensor device is preferably adapted to sense at least one climateparameter from the group comprising temperature, pressure, humidity,airspeed and the presence of toxic elements in fume. These measured aircharacteristics are used for manipulating the inflowing air into theinterior space, so that it is ensured that the biological samples areprocessed in a controlled ambient environment and that it is ensuredthat the samples do not dry out or are otherwise being deteriorated.

The sensor device may comprise internal sensors located inside theinterior space. Alternatively, the sensor may comprise external sensorslocated outside the interior space, such as at or inside an airinlet/outlet manifold, in a laboratory facility accommodating theapparatus, or outside the building accommodating the laboratory.

In the preferred embodiment, the cover is at least one openable hood.The cover is an integrated part of the apparatus, e.g. a hinged hoodwhich may be swung open. An automatic lock may be provided to preventany opening during the processing.

In an embodiment, the cover is a plurality of covers arranged to cover aplurality of sections of the apparatus, such as at least one biologicalsample accommodated on a carrier in the at least one processing section.Hereby, different environments may be created for different samples. Aplurality of interior spaces may be defined by a plurality of covers inthe apparatus, each interior space including at least one sectionarranged for comprising at least one sample on a carrier and/or at leastone section arranged for comprising at least one reagent in a container.

The climate control device may be arranged to controlling the climate ineach interior space, comprising at least one sample on a carrier,according to a sample processing protocol defined for that particularsample. In an embodiment of the invention, the climate control devicereceives input signals from internal and/or external sensors, and arearranged to control the climate in each interior space, according to theinput signals. The climate control device may then preferably connectedfor data communication with a data processing device, such as acomputer, wherein the protocol for the processing of the particularsample is stored, and where from control data are provided to theclimate control device. Hereby, an automatic climate control is providedfor the sample processing, whereby it may be possible to provide aselected air environment for a particular sample processing protocol.

In a preferred embodiment of the invention, the hood cover is providedwith one or more seal elements to provide an air-tight seal between thecover and the housing. Hereby, the sub-pressure need not be present or ahigher pressure inside may be provided for achieving a more preciseclimate control inside the apparatus.

The exchange of air between the interior space and the surroundings maybe carried out via an inlet and an outlet. In an embodiment of theinvention, the inlet may be provided for supplying air into the interiorspace including an air inlet opening in the housing, and wherein airmanipulation device are provided in addition to said inlet means toadapt the inflowing air with predetermined characteristics. Hereby, theinside climate of the air in the interior space may be accuratelycontrolled.

According to the present invention, a method and an apparatus isprovided which allows air containing the fumes to be removed to theexterior or removed on a filter device before the cleaner air is beingrecycled.

Also, it should be understood, that the air drawn into the interiorspace in addition to be temperature controlled by heating or cooling,also may be added humidity by spraying water droplets or using a filterdevice, or added other components, like nitrogen gas, carbondioxide orinert gasses to control the environment in the hood.

In one preferred embodiment, the inlet air is drawn through a humidfilter device to ensure high and uniform humidity in the chamber.

In another preferred embodiment, the humidity is controlled by sprayingwater droplets or having a water surface.

In yet another preferred embodiment, recycled air is drawn throughfilters to remove fumes and filters to adjust the humidity.

In yet another preferred embodiment, the humidity is controlled to neverbe below a predetermined level, to prevent drying out of the sample.

Also, disfectantes, UV protectants or other compounds could be added tothe inlet air to prevent microbial growth or discolouring.

It should be understood that by controlling the environment by thepresent invention, the mechanical and electrical parts are alsoprotected from corrosion and wear. Also, by an apparatus according tothe invention the air may be moved around inside the interior spacewhich ensures uniform and controllable temperature control.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is described with reference to a preferred embodiment withreference to the drawings, in which:

FIG. 1 is a schematic perspective view of a staining apparatus accordingto the preferred embodiment of the invention;

FIG. 2 is a top view of the work area in the staining apparatus shown inFIG. 1;

FIG. 3 is a schematic side view of the staining apparatus of FIG. 1; and

FIG. 4 is an example of a ventilation assembly mountable in the housingin an apparatus according to the invention.

BEST MODES FOR CARRYING OUT THE INVENTION

A staining apparatus 1 according to the invention is shown in thefigures. The staining apparatus 1 comprises a rectangular housing frame4 surrounding a reagent station 2 comprising an array of reagent bottlecompartments wherein each compartment a reagent vial 3 is placed, and afirst and second slide sections 5 wherein a number of separate rackassemblies 11 is placed, potentially in some embodiments in one or moredrawer assemblies 6, and where each rack assembly 11 accommodates anumber of microscope slides 7 mounted side by side in the rack assembly.In the embodiment shown, each rack may hold up to 8 slides, but the rackmay be designed to hold any suitable number of slides. With eight racksarranged side by side, the shown embodiments may hold up to 64 slides 7each having a biological sample, e.g. a tissue mounted on the upper sideof the slide, so that reagent may be applied from above to the sample oneach slide.

A sensor may be provided in some embodiments that may automaticallyidentify information from one or more slides 7. In some embodiments,protocol information may be provided by an adaptive sample processingcontrol system. The sample processing system may process one or moreslides 7, or one or more batches of slides 7, concurrently,sequentially, or in any other temporal fashion, potentially inaccordance with protocol information provided by a slide having a sampleor provided by the adaptive sample processing control system. Samplebatches or individual slides 7 may be inserted or removed duringprocessing protocol steps by the control and monitoring accomplished bythe adaptive sample processing control system.

In some embodiments, the system may comprise independent and redundantslide staining modules, such as drawer assemblies 6. Throughput is basedon time to first result with the system allowing access to completedslides 7 as soon as a staining module has completed the scheduledstaining tasks. The multiple independent and redundant staining modulesallow for both continuous and batch processing of slides 7.Additionally, each independent staining module also allows for theindependent pre-treatment and staining of each slide. A carrier rackassembly 11 may be used to introduce slides 7 to be processed into thedrawer 6, the drawer, carrier rack assembly 11, and components thereofforming a stain module. The slides 7 may occupy one or more positions ofthe carrier rack assembly 11, such as at carrier retention devices, upto the capacity of the carrier rack assembly 11 with the potential foreach slide being processed independently of other slides 7 configuredwith carrier rack assembly 11. Embodiments of the stain modules,drawers, rack assemblies, and components thereof are also shown inFIG. 1. FIG. 1 also provides other embodiments of system features, suchas an embodiment of the arm 20 and the component features of the arm.

Carrier rack assemblies 11 having one or more slides 7 may be introducedinto the staining modules by introduction into drawers 6 one at a timeor in any combination until all staining modules are occupied. There maybe no restrictions as to the order, number or timing of when the carrierrack assemblies 11 are introduced into the system, the system allowingfor adaptive scheduling of sample loading. Staining modules, and in someembodiments the drawers 6 of the staining modules, will lock out accessto the slides 7 during the processing period and may release them to theoperator upon completion of the staining process on the last slide. Insome embodiments, the order in which the carrier rack assemblies 11 arereleased is dependent on the time required to process the last slide ofthe rack assembly. Slides 7 may be processed in the most time efficientmanner independently of the order to which they were introduced into thesystem.

Multiple drawers 6 allow for one or a plurality of sample processingprotocols to be performed by the system. Past efforts at sampleprocessing, as previously described, may have been limited to processingsequences for an entire batch of carriers within the system. The presentinvention, however, in part by providing a plurality of drawers 6 andcarrier rack assemblies 11, may allow for multiple batch processing.including real-time or adaptive capabilities for multiple batchprocessing as further described below.

Indicator-elements may be provided to indicate a status of the drawers 6and the carriers or materials within each drawer for an operator of thesystem. In one embodiment, visual indicators, such as light emittingdiodes in preferred embodiments, indicate if a drawer is availableduring operation of the sample processing system, and may indicateconditions such as a locked or open condition of a corresponding drawer,6 carrier capacity status of the drawer or of a carrier rack assembly 11within the drawer 6, and chemical status of the sample processingsystem, such as reagent loading status or capacity. A warning indicationmay be given by the indicator elements, as well as other indicativesignals. One or a plurality of sensors may be utilized to determine thestatus of the drawer as indicated by the indicator elements and tofurther provide processing status as further described below.Furthermore, adaptive scheduling of sample and slide insertion andremoval into the system may be accommodated on an on-going basisthroughout operation of the sample processing system.

A robot arm 20 for moving a probe 10 in X and Y (as well as Z) directionas indicated by the arrows X and Y is arranged above the frame 4 of thestaining apparatus. The robot arm 20 may is therefore position the probe10 above all reagent vials 3 as well as above all the microscope slides7, and may further operate the probe 10 to aspirate portions of reagentcontained in any of the vials 3, to transfer the portion of reagent andapply it to any of the slides 7 in order to provide a selected stainingor treatment of the sample on each slide 7. By use of suitable control,e.g. a computer (not shown) having the appropriate software and inputdata for the purpose, this staining apparatus 1 is able to automaticallystain or treat samples requiring different staining or treatmentreagents and processes.

As shown in FIG. 1, the probe 10 is accommodated in a robotic head 22and is manipulated by the robot arm 20. The probe 10 is raised to anupper position (in a Z direction) where it is clear of the vials 3underneath the probe 10, but the robot comprises means in the robotichead 22 for lowering the probe 10 in order to dip the probe tip into thecontent of a selected reagent vial 3 and to aspirate a selected amountof reagent for the selected staining or treatment process. The robotichead 22 may also be provided with a CCD camera 25, in some embodimentsconfigured to point downwards. The camera is utilised to determinestatus information of the slides and the reagent bottles and otherfeatures of the apparatus in the work area, for example readinginformation which may or may not be encrypted, that is provided on areagent container to determine the reagent type and the reagent locationwithin the system. The camera may also determine status of the tissuesample carriers, for example the location of a particular slide,informational indicia, such as which may be converted into an encryptedformat, that indicate information about the tissue sample presented onthe slide or the processing protocol to be performed.

The staining apparatus 1 of the present embodiment further comprises aprobe washing station 8 and a reagent mixer 9, and the robot arm 20 isfurthermore arranged to transfer the probe 10 to the washing station 8as well as to the reagent mixer 9.

As shown in FIG. 3, the apparatus 1 is provided with an openable hoodcover 40, which is pivotably attached to the frame housing 4. The hood40 is shown in a closed position and an open position 40′ is indicatedin dotted lines in the figure.

In the bottom of the frame housing 4, the slide rack assemblies 11,potentially in some embodiments in one or more drawer assemblies 6 areprovided. An interior space 120 is defined by this hood cover 40 and theframe 4. The staining sections 5 and the reagent station 2 are arrangedsuch that they are accessible by the robotic arm 20 via the equipmentarranged on the robotic head 22.

A climate control device 121 is provided for controlling the pressureand potentially also the temperature and the humidity of the air in theinterior space 120 inside the apparatus 1. This climate control 121includes an outlet 122 and an inlet 123 allowing for an exchange of airin a controlled manner. Exhausted air from the interior space may bedirected to a collection storage or disposed of in other mannersdepending on the requirements on the location of the apparatus. Theexhausted air may—in particular in some staining or otherprocesses—include volatile fumes or other toxic or unwanted fumes fromthe reagents and other liquids used for the processing of the biologicalsamples.

The ambient air in the interior space 120 is drawn through the rackassembly 11 of the drawer assembly 6 in the staining sections 5. In thedrawer assembly 6, other processing devices are preferably alsoprovided, such as pretreatment tanks in which the biological specimensarranged on slides may be immersed in a pretreatment liquid which isoften heated to a processing temperature. By drawing the fumes out ofthe interior space 120 at a location close to the heating sources andbelow the level in which the slides are arranged, the fumes areessentially prevented from diffuse to widely in the interior space,whereby the risk of such fumes coming into unwanted contact withbiological samples, other reagents or processing liquids may be avoided.

Besides maintaining a slight sub-pressure inside the hood, the climatecontrol may also be adapted to controlling the temperature and thehumidity inside the apparatus, so that such climatic conditions do notinterfere with the staining processes. Hereby, the apparatus may easilybe adapted to changes in the environment, such as seasonal changes,temperature changes, just as the apparatus according to the inventionmay be able to adapt itself to a specific location, e.g. adapt todifference in altitude, etc.

The temperature, humidity, airflow rate and/or other environmentalfactors can be controlled by a feed back mechanism from a sensor device,such as one or more sensors 125 arranged in the hood or elsewhere insidethe interior space and/or external sensors 125, which may beadvantageous in order to compensate for external influences such as hightemperature or extremely dry climate in local areas having extremeclimate variations.

The system may further have the ability to vent toxic and or flammablefumes from inside the cabinet portions or enclosure to exit ports thatcan be connected to an external system vent or hood, such as vent 160.Embodiments may comprise exit ports from the internal enclosure of thesystem and exit ports from the bulk fluid containers of the system, suchas reagent containers. Fumes may be isolated and removed from variouscompartments within the system. An environmental control systemaddresses the system's ventilation to ensure the evacuation of volatileorganic vapours, keeping the concentration of these materials belowestablished toxic and explosive limits.

In some embodiments, a ventilation system such as that shown in FIGS. 3and 4 will draw hazardous fumes from the vicinity of each processingtank in the drawer assemblies 6 by an exhaustion device that maycomprise dedicated ducts 122, 123. These ducts will feed a manifold 121running along the rear of the instrument. The ventilation system mayfurther comprise a fan in an air inlet opening in the housing frame 4through which air may be exchanged. A separate ventilation system for anelectronic chassis of the system may be similarly isolated havingindependent air input and output vents. Each of these systems hasindependent air input and output air vents. At one end of the manifold,a centrifugal blower will exhaust the fumes to an exit port that may beconnected to the facility hood/exhaust system.

In FIG. 4, a ventilation assembly 80 for mounting in the apparatus isshown. Through this ventilation assembly 80 air may be exchanged betweenthe interior space 120 and the surroundings. In addition to the inletand outlet ducts 122, 123, air manipulation devices 81, 82 may bearranged. These air manipulation devices may include moisture control,air pressure and air flow regulation in order to control the environmentin the interior space automatically in response to sensor 125 readingsinside the interior space.

Above, the apparatus according to the invention is described accordingto some preferred explanatory embodiments. However, it is realised bythe invention that many other variations and equivalents of theapparatus may be carried out without departing from the scope of theinvention as specified in the accompanying claims.

As can be easily understood from the foregoing, the basic concepts ofthe present invention may be embodied in a variety of ways. It involvesboth sample processing techniques as well as various systems,assemblies, and devices to accomplish sample processing, input, andother functions. In this application, the sample processing techniquesare also disclosed as part of the results shown to be achieved by thevarious systems, assemblies, and devices described and as steps whichare inherent to utilization. They should be understood to be the naturalresult of utilizing the devices as intended and described. In addition,while some devices are disclosed, it should be understood that these notonly accomplish certain methods but also can be varied in a number ofways. Importantly, as to all of the foregoing, all of these facetsshould be understood to be encompassed by this disclosure.

The discussion included in this application is intended to serve as abasic description. The reader should be aware that the specificdiscussion may not explicitly describe all embodiments possible; manyalternatives are implicit. It also may not fully explain the genericnature of the invention and may not explicitly show how each feature orelement can actually be representative of a broader function or of agreat variety of alternative or equivalent elements. Again, these areimplicitly included in this disclosure. Where the invention is describedin device-oriented terminology, each element of the device implicitlyperforms a function. Importantly, neither the description nor theterminology is intended to limit the scope of the claims which may beincluded at any time.

It should also be understood that a variety of changes may be madewithout departing from the essence of the invention. Such changes arealso implicitly included in the description. They still fall within thescope of this invention. A broad disclosure encompassing both theexplicit embodiment(s) shown, the great variety of implicit alternativeembodiments, and the broad methods or processes and the like areencompassed by this disclosure and may be relied upon at any time.

Further, each of the various elements of the invention and claims mayalso be achieved in a variety of manners. This disclosure should beunderstood to encompass each such variation, be it a variation of anembodiment of any apparatus embodiment, a method or process embodimentor even merely a variation of any element of these. Particularly, itshould be understood that as the disclosure relates to elements of theinvention, the words for each element may be expressed by equivalentapparatus terms or method terms—even if only the function or result isthe same. Such equivalent, broader, or even more generic terms should beconsidered to be encompassed in the description of each element oraction. Such terms can be substituted where desired to make explicit theimplicitly broad coverage to which this invention is entitled. As butone example, it should be understood that all actions may be expressedas a means for taking that action or as an element which causes thataction. Similarly, each physical element disclosed should be understoodto encompass a disclosure of the action which that physical elementfacilitates. Regarding this last aspect, as but one example, thedisclosure of a “retention element” should be understood to encompassdisclosure of the act of “retaining”—whether explicitly discussed ornot—and, conversely, were there effectively disclosure of the act of“retaining”, such a disclosure should be understood to encompassdisclosure of a “retention element” and even a “means for retaining”. Itshould also be understood that in jurisdictions where specific languagemay be construed as limiting, as but one example in the United Stateswhere some interpretations of “means for” elements can be construednarrowly, broader equivalent language may be used and should beunderstood as encompassed by this specification. Such changes andalternative terms are to be understood to be explicitly included in thedescription.

Any patents, patent applications, publications, or other referencesmentioned in this application for patent are hereby incorporated byreference. In addition, as to each term used it should be understoodthat unless its utilization in this application is inconsistent withsuch interpretation, common dictionary definitions should be understoodas incorporated for each term and all definitions, alternative terms,and synonyms such as contained in the Random House Webster's UnabridgedDictionary, second edition are hereby incorporated by reference as wellas the definitions presented by searchStorage.com, such to be consideredas representing the meaning of the terms as understood by computerprofessionals. Finally, any priority case for this application is herebyappended and hereby incorporated by reference.

Thus, the applicant(s) should be understood to have support to claim atleast i) each of the sample processing systems and subsystems as hereindisclosed and described, ii) the related methods disclosed anddescribed, iii) similar, equivalent, and even implicit variations ofeach of these systems, assemblies, devices and methods, iv) thosealternative designs which accomplish each of the functions shown as aredisclosed and described, v) those alternative designs and methods whichaccomplish each of the functions shown as are implicit to accomplishthat which is disclosed and described, vi) each feature, component, andstep shown as separate and independent inventions, vii) the applicationsenhanced by the various systems or components disclosed, viii) theresulting products produced by such systems or components, and ix)methods and systems, assemblies, devices, and apparatuses substantiallyas described hereinbefore and with reference to any of the accompanyingexamples, x) the various combinations and permutations of each of theelements disclosed, xi) each potentially dependent claim or concept as adependency on each and every one of the independent claims or conceptspresented, xii) processes performed with the aid of or on a computer asdescribed throughout the above discussion, xiii) a programmable systemas described throughout the above discussion, xiv) a computer readablememory encoded with data to direct a computer comprising means orelements which function as described throughout the above discussion,xv) a computer configured as herein disclosed and described, xvi)individual or combined subroutines and programs as herein disclosed anddescribed, xvii) the related methods disclosed and described, xviii)similar, equivalent, and even implicit variations of each of thesesystems and methods, xix) those alternative designs which accomplisheach of the functions shown as are disclosed and described, xx) thosealternative designs and methods which accomplish each of the functionsshown as are implicit to accomplish that which is disclosed anddescribed, xxi) each feature, component, and step shown as separate andindependent inventions, and xxii) the various combinations andpermutations of each of the above.

Further, if or when used, the use of the transitional phrase“comprising” or the like is used to maintain the “open-end” claimsherein, according to traditional claim interpretation. Thus, unless thecontext requires otherwise, it should be understood that the term“comprise” or variations such as “comprises” or “comprising” or thelike, are intended to imply the inclusion of a stated element or step orgroup of elements or steps but not the exclusion of any other element orstep or group of elements or steps. Such terms should be interpreted intheir most expansive form so as to afford the applicant the broadestcoverage legally permissible.

Any claims set forth at any time are hereby incorporated by reference aspart of this description of the invention, and the applicant expresslyreserves the right to use all of or a portion of such incorporatedcontent of such claims as additional description to support any of orall of the claims or any element or component thereof, and the applicantfurther expressly reserves the right to move any portion of or all ofthe incorporated content of such claims or any element or componentthereof from the description into the claims or vice-versa as necessaryto define the matter for which protection is sought by this applicationor by any subsequent continuation, division, or continuation-in-partapplication thereof, or to obtain any benefit of, reduction in feespursuant to, or to comply with the patent laws, rules, or regulations ofany country or treaty, and such content incorporated by reference shallsurvive during the entire pendency of this application including anysubsequent continuation, division, or continuation-in-part applicationthereof or any reissue or extension thereon.

1. An apparatus for automatic processing of at least one biologicalsample accommodated on at least one slide, comprising: a housing frame;at least one slide; a plurality of drawers within the housing, eachdrawer comprising a respective carrier rack for supporting the at leastone slide; a robotic reagent dispensing head within the housing thatperforms ongoing robotic processing, including dispensing of reagents,at least one sample processing section within the housing foraccommodating at least one of the plurality of drawers; a cover forprotecting said at least one sample processing section in said housing,said cover enclosing the sample processing section and defining aninterior space between the housing and the cover; at least one climatecontrol device for controlling the environment within said interiorspace defined by the cover; a sensor device for providing feedbacksignals to the climate control device; and a data processing deviceconfigured to control the at least one climate control device, whereinthe data processing device comprises a processing protocol includinginstructions to apply a predetermined amount of reagents to in apredetermined sequence on the at least one slide, wherein a first draweris configured to permit a first sample accommodated in the first drawer,for which the processing is completed, to be removed from the apparatuswithout opening the cover or interrupting the ongoing robotic processingof a second sample in a second drawer, and wherein the second drawer isconfigured to permit the second sample accommodated in the seconddrawer, to be inserted into the apparatus without opening the cover orinterrupting the dispensing of reagents onto the first sample, in thefirst drawer, with the robotic reagent dispensing head.
 2. An apparatusaccording to claim 1, wherein the sensor device is adapted to sense atleast one climate parameter from the group consisting of temperature,pressure, humidity, airspeed and the presence of toxic elements in fume.3. An apparatus according to claim 1, wherein the sensor devicecomprises internal sensors located inside the interior space.
 4. Anapparatus according to claim 1, further comprising an air inlet/outletmanifold, wherein the sensor device comprises external sensors locatedat or inside the air inlet/outlet manifold, in a laboratory facilityaccommodating the apparatus, or outside a building accommodating thelaboratory.
 5. An apparatus according to claim 1, wherein the covercomprises at least one openable hood pivotably attached to the housingframe.
 6. An apparatus according to claim 1, wherein the cover isintegral with the housing frame.
 7. An apparatus according to claim 1,wherein the cover comprises a plurality of covers arranged to cover aplurality of sections of the apparatus, wherein the plurality ofsections includes the at least one sample processing section.
 8. Anapparatus according to claim 7, wherein a plurality of interior spacesof the apparatus is defined by said plurality of covers, each interiorspace being defined as the volume located between the cover and thehousing and each interior space including at least one sectioncomprising at least one sample on the at least one slide and/or at leastone section comprising at least one reagent in a container.
 9. Anapparatus according to claim 8, wherein the at least one climate controldevice controls the climate of the at least one biological sample on theat least one slide in each interior space according to the processingprotocol defined for that particular sample.
 10. An apparatus accordingto claim 9, wherein the sensor device comprises internal sensors andexternal sensors, and wherein the at least one climate control devicereceives input signals from the internal and/or external sensors andcontrols the climate in each interior space according to the inputsignals.
 11. An apparatus according to claim 8 wherein the dataprocessing device data processing device comprises a computer.
 12. Anapparatus according to claim 1, wherein the at least one climate controldevice includes pressure control device for controlling at least thepressure and configured to provide a slight sub-pressure within theinterior space.
 13. An apparatus according to claim 1, wherein the atleast one climate control device includes a pressure control device forcontrolling at least the pressure and configured to provide a slightlyhigher pressure within the interior space.
 14. An apparatus according toclaim 1, wherein the at least one climate control device includes ahumidity controller within the interior space.
 15. An apparatusaccording to claim 1, wherein the at least one climate control deviceincludes a temperature control device for controlling the ambienttemperature of the air within the interior space.
 16. An apparatusaccording to claim 1, wherein the climate control device comprises aventilation system with an exhaustion device having a plurality of ductsfor exchanging the air in the interior space with a manifold in thehousing frame.
 17. An apparatus according to claim 16, wherein theventilation system comprises a centrifugal blower in an air inletopening in the manifold of the housing frame through which air may beexchanged.
 18. An apparatus according to claim 17, further comprising atleast one air manipulation device with the air inlet opening foradapting the air temperature, pressure, air flow rate, and humidity ofthe inflowing air into the apparatus.
 19. An apparatus according toclaim 1, wherein the climate control device comprises an exhaustiondevice with an outlet for removing fumes from the interior space.
 20. Anapparatus according to claim 1, wherein the climate control device is adevice for recycling air for humidity, temperature, and toxic control, adevice for removing toxic elements from the air to be recycled, a devicefor supplying humidity to the air to be recycled, or a heater/coolingdevice for controlling the temperature of the air to be recycled.
 21. Anapparatus according to claim 20, wherein the device configured torecycle air comprises a filter capable of cleaning and/or humidifyingthe air.
 22. An apparatus according to claim 19, wherein the outlet ispositioned below a level in which the at least one slide is accommodatedand said exhaustion device is adapted to draw air through the outlet.23. An apparatus according to claim 19, wherein the outlet is positionedabove a level in which the at least one slide is accommodated and saidexhaustion device is adapted to draw air through the outlet.
 24. Anapparatus according to claim 1, wherein said cover is provided with atleast one seal element to provide an air tight seal between the covermeans and the housing.
 25. An apparatus according to claim 1, whereinthe housing frame comprises at least one air inlet opening adapted tosupply air into the interior space, and wherein the climate controldevice comprises an air manipulation device configured to adapt theinflowing air with predetermined characteristics, the air manipulationdevice being provided in the at least one air inlet opening.
 26. Anapparatus according to claim 25, wherein said air manipulation devicecomprises a humid filter device adapted to draw inflowing air throughthe humid filter device and provide high and uniform humidity in thechamber.
 27. An apparatus according to claim 25, wherein the airmanipulation device sprays water droplets or has a water surface andthereby controls humidity.
 28. An apparatus according to claim 25,wherein the air manipulation device comprises an air recycling devicewith filters, the recycled air being drawn through the filters to removefumes and adjust the humidity.
 29. An apparatus according to claim 25,wherein the air manipulation device controls the humidity to never bebelow a predetermined level, to prevent drying out of the sample.
 30. Anapparatus according to claim 25, wherein the air manipulation devicecomprises an air additive supply device in the at least one air inletopening, the air additive supply device adding disinfectants, UVprotectants or other compounds to the inlet air to prevent microbialgrowth or discolouring.
 31. An apparatus according to claim 25, whereinthe air manipulation device comprises an air additive supply device inthe at least one air inlet opening, the air additive supply deviceadding fluids from the group consisting of reagents, neutral gas,oxygen, carbon dioxide, nitrogen, water droplets, and formamide.
 32. Anapparatus according to claim 1, wherein the sensor device registers oneor more parameters of the air in interior space of the apparatus, saidsensor device being arranged in a vicinity of the cover and/or in avicinity of the at least one slide on the carrier rack.
 33. An apparatusfor automatic staining of at least one biological sample accommodated onat least one slide, comprising: a housing frame; at least one slide; aplurality of drawers within the housing, each drawer comprising arespective carrier rack for supporting the at least one slide; a roboticreagent dispensing head within the housing that performs ongoing roboticprocessing, including dispensing of reagents, at least one stainingsection within the housing configured to accommodate at least one of theplurality of drawers; a cover for protecting said at least one stainingsection in said housing, said cover enclosing the staining section anddefining an interior space between the housing and the cover; at leastone climate control device configured to control the environment withinsaid interior space defined by the cover; a sensor device providingfeedback signals to the climate control device; and a data processingdevice configured to control the at least one climate control device,wherein the data processing device comprises a processing protocolincluding instructions to apply a predetermined amount of reagents to ina predetermined sequence on the at least one slide, wherein a firstdrawer is configured to permit a first sample accommodated in the firstdrawer, for which the processing is completed, to be removed from theapparatus without opening the cover or interrupting the ongoing roboticprocessing of a second sample in a second drawer, and wherein the seconddrawer is configured to permit the second sample accommodated in thesecond drawer, to be inserted into the apparatus without opening thecover or interrupting the dispensing of reagents onto the first sample,in the first drawer, with the robotic reagent dispensing head.
 34. Anapparatus according to claim 33, wherein the sensor device is adapted tosense at least one climate parameter from the group consisting oftemperature, pressure, humidity, airspeed and the presence of toxicelements in fume.
 35. An apparatus according to claim 33, wherein thesensor device comprises internal sensors located inside the interiorspace.
 36. An apparatus according to claim 33 further comprising an airinlet/outlet manifold, wherein the sensor device comprises externalsensors located at or inside the air inlet/outlet manifold, in alaboratory facility, accommodating the apparatus, or outside a buildingaccommodating the laboratory.
 37. An apparatus according to claim 33,wherein the cover comprises at least one openable hood pivotablyattached to the housing frame.
 38. An apparatus according to claim 33,wherein the cover is integral with the housing frame.
 39. An apparatusaccording to claim 33, wherein the cover comprises a plurality of coversarranged to cover a plurality of sections of the apparatus, wherein theplurality of sections includes the at least one staining section.
 40. Anapparatus according to claim 39, wherein a plurality of interior spacesof the apparatus is defined by said plurality of covers, each interiorspace being defined as the volume located between the cover and thehousing, and each interior space including at least one sectioncomprising at least one sample on the at least one slide and/or at leastone section comprising at least one reagent in a container.
 41. Anapparatus according to claim 40, wherein the at least one climatecontrol device controls the climate of the at least one biologicalsample on the at least one slide in each interior space according to theprocessing protocol defined for that particular sample.
 42. An apparatusaccording to claim 41, wherein the sensor device comprises internalsensors and external sensors, and wherein the at least one climatecontrol device receives input signals from the internal and/or externalsensors and controls the climate in each interior space according to theinput signals.
 43. An apparatus according to claim 40, wherein the dataprocessing device data processing device comprises a computer.
 44. Anapparatus according to claim 33, wherein the at least one climatecontrol device includes a pressure control device for controlling atleast the pressure and configured to provide a slight sub-pressurewithin the interior space.
 45. An apparatus according to claim 33,wherein the at least one climate control device includes a pressurecontrol device for controlling at least the pressure and configured toprovide a slightly higher pressure within the interior space.
 46. Anapparatus according to claim 33, wherein the at least one climatecontrol device includes a humidity controller within the interior space.47. An apparatus according to claim 33, wherein the at least one climatecontrol, device includes a temperature control device for controllingthe ambient, temperature of the air within the interior space.
 48. Anapparatus according to claim 33, wherein the climate control devicecomprises a ventilation system with an exhaustion device having aplurality of ducts for exchanging the air in the interior space with amanifold in the housing frame.
 49. An apparatus according to claim 48,wherein the ventilation system comprises a centrifugal blower in an airinlet opening in the manifold of the housing frame through which air maybe exchanged.
 50. An apparatus according to claim 49, further comprisingat least one air manipulation device with the air inlet opening foradapting the air temperature, pressure, air flow rate, and humidity ofthe inflowing air into the apparatus.
 51. An apparatus according toclaim 33, wherein the climate control device comprises an exhaustiondevice with an outlet capable, of removing fumes from the interiorspace.
 52. An apparatus according to claim 33, wherein the climatecontrol device is a device capable of recycling air for humidity,temperature; and toxic control, a device capable of removing toxicelements from the air to be recycled, a device capable of supplyinghumidity to the air to be recycled, or a heater/cooling device capableof controlling the temperature of the air to be recycled.
 53. Anapparatus according to claim 52, wherein the device configured torecycle air comprises a filter capable of cleaning and/or humidifyingthe air.
 54. An apparatus according to claim 51, wherein the outlet ispositioned below a level in which the at least one slide is accommodatedand said exhaustion device is adapted to draw air through the outlet.55. An apparatus according to claim 51, wherein the outlet is positionedabove a level in which the at least one slide is accommodated and saidexhaustion device is adapted to draw air through the outlet.
 56. Anapparatus according to claim 33, wherein said cover is provided with atleast one seal element to provide an air tight seal between the covermeans and the housing.
 57. An apparatus according to claim 33, whereinthe housing frame comprises at least one air inlet opening adapted tosupply air into the interior space, and wherein the climate controldevice comprises an air manipulation device configured to adapt theinflowing air with predetermined characteristics, the air manipulationdevice being provided in the at least one air inlet opening.
 58. Anapparatus according to claim 57, wherein said air manipulation devicecomprises a humid filter device adapted to draw inflowing air throughthe humid filter device and provide high and uniform humidity in thechamber.
 59. An apparatus according to claim 57, wherein the airmanipulation device sprays water droplets or has a water surface andthereby controls humidity.
 60. An apparatus according to claim 57,wherein the air manipulation device comprises an air recycling devicewith filters, the recycled air being drawn through the filters to removefumes and adjust the humidity.
 61. An apparatus according to claim 57,wherein the air manipulation device controls the humidity to never bebelow a predetermined level, to prevent drying out of the sample.
 62. Anapparatus according to claim 57, wherein the air manipulation devicecomprises an air additive supply device in the at least one air inletopening, the air additive supply device adding disinfectants, UVprotectants or other compounds to the inlet air to prevent microbialgrowth or discolouring.
 63. An apparatus according to claim 57, whereinthe air manipulation device comprises an air additive supply device inthe at least one air inlet opening, the air additive supply deviceadding fluids from the group consisting of reagents, neutral gas,oxygen, carbon dioxide, nitrogen, water droplets, and formamide.
 64. Anapparatus according to claim 33, wherein the sensor device registers oneor more parameters of the air in interior space of the apparatus, saidsensor device being arranged in a vicinity of the cover and/or in avicinity of the at least one slide on the carrier rack.